title: Integrated pathways of parkin control over mitochondrial maintenance - relevance to Parkinson's disease pathogenesis.
abstract: Mitochondrial dysfunction and oxidative stress are considered among the main molecular mechanisms implicated in Parkinson's disease (PD) pathogenesis. Here, we focus on the deficiency of PARK2 and its product parkin, which is relevant to both familial and sporadic PD pathogenesis. Parkin emerges as an important regulator of processes that maintain mitochondrial quality. We focus on the parkin-dependent aspects of mitochondrial biogenesis, including mtDNA replication, transcription, mitophagy, mitochondrial fusion, fission, and transport. We discuss possible underlying molecular mechanisms, exerted by parkin in cooperation with other mitochondrial maintenance factors such as TFAM, PGC-1alpha, mortalin, HSP70/HSC70 and LRPPRC, all of them implicated in PD pathogenesis. We review numerous models of lipopolysaccharide toxicity that demonstrate how mitochondrial biogenesis and mitophagy are induced simultaneously to cope with mitochondrial dysfunction. The spatial and temporal interdependence of mitochondrial quality pathways underscores the importance of an integrative approach for future studies.
authors.affiliation: Laboratory of Neurogenetics, Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland. kasiawal@libero.it.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gaweda-Walerych
authors.forename: Cezary
authors.initials: C
authors.lastname: Zekanowski
mesh_terms: D006801:Humans; D008928:Mitochondria / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000209:etiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; D020033:Protein Isoforms; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein